1
880
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 8, August, 2003
Mete et al.
1
Thus, we described a method for the easy and conveꢀ
1510, 1458, 1413, 1041. The H NMR and IR data are in agreeꢀ
1
8
ment with the data given in the literature.
ꢀAminoꢀ3ꢀhydroxybutyric acid (1). Amine hydrochloride 6
2.20 g, 16 mmol) was dissolved in 98% H SO (2 mL, 38 mmol)
and heated for 5 min. Then it was diluted with 20 mL of water
and heated to reflux for 3 h. After being cooled, the solution was
nient synthesis of (R,S)ꢀGABOB via allyl cyanide, a comꢀ
mercially available and cheap starting material, in four
steps, giving an overall yield of 38%.
4
(
2
4
Experimental
made basic with excess BaCO and heated for 1 h. Then it was
3
filtered with suction and exactly neutralized with several drops
of 2% H SO . The water was evaporated, and the resulting mixꢀ
Melting points were determined on a Büchi 530 instrument
and were not corrected. IR spectra were recorded on a Mattson
2
4
+
ture was filtered through Amberlite IRꢀ120 (H ) eluting with a
0% NH solution. The eluate was concentrated to give 4ꢀaminoꢀ
1
1
000 FTꢀIR spectrophotometer in KBr pellets or in thin layer.
3
1
13
3ꢀhydroxybutyric acid (1) (1.44 g, 75%) as a white solid, m.p.
H and C NMR spectra were obtained on a Varian spectromꢀ
o
1
13
214—215 C (recrystallized from an EtOH—water mixture;
eter (working frequency 200 and 50 MHz for H and C, reꢀ
spectively).
o
1
cf. Ref. 7a: m.p. 214 C). H NMR (D O), δ: 4.10 (m, 1 H,
2
3
H(3)); 3.07 (dd, A part of ABХ system, 1 H, H (4), J = 3.2 Hz,
J = 13.1 Hz); 2.85 (dd, B part of ABХ system, 1 H, H (4), J =
.4 Hz, 2J = 13.1 Hz); 2.35 (d, 2 H, C(2)H , J = 6.8 Hz).
С NMR (D O), δ: 183.1 (C(1)), 70.1 (C(3)), 48.8 (C(4)), 46.8
C(2)). IR (KBr), ν/cm : 3444, 3066—2576, 2132, 1631, 1562,
407, 1265, 1118, 1064, 1022, 975. The H NMR, C NMR,
Caution! Allyl cyanide may be harmful if absorbed through
the skin. It may cause eye and skin irritation. It may also cause
respiratory and digestive tract irritation. Therefore, a fume hood
should be used during experiments and gloves should be worn.
a
2
3
b
9
2
1
3
2
–
1
(
1
2
ꢀOxiranylacetonitrile (4). MCPBA (44.13 g, 70%,
1
13
1
1
79 mmol) was added to a solution of allyl cyanide 3 (12 g,
79 mmol) in CHCl3 (140 mL). The resulting solution was
sonicated in an ultrasonic bath (47 kHz) for two days. A satuꢀ
and IR data are in agreement with the data given in the litꢀ
1
9
erature.
rated aqueous solution of NaHSO (100 mL) was added to reꢀ
duce unreacted MCPBA. The organic phase was separated,
washed with saturated aqueous NaHCO3 (2×50 mL), and
3
This work was financially supported by the Ataturk
University (Grant 2002/57).
dried over anhydrous MgSO . Evaporation of the solvent gave
4
epoxynitrile 4 17 as a colorless oil (9.07 g, 61%). H NMR
1
References
(
4
CDCl ), δ: 3.15—3.07 (m, 1 H, H(3)); 2.77 (t, 1 H, H (4), J =
.3 Hz); 2.70—2.56 (m, 3 H, H (4), H (2), H (2)). С NMR
b a b
3
a
13
(
CDCl ), δ: 115.3 (C(1)), 46.3 (C(3) or C(4)), 45.7 (C(4) or
1. (a) D. S. Bose and M. K. Gurjar, Synth. Commun., 1989, 19,
3313; (b) Y. N. Bubnov, L. I. Lavrinovich, A. Y. Zykov, and
A. V. Ignatenko, Mendeleev Commun., 1992, 86.
2. (a) E. GarcíaꢀFlores and R. Farías, Stereotact. Funct.
Neurosurg., 1997, 69, 243; (b) R. Chemello, D. Giaretta,
A. Pellegrini, and G. Testa, Riv. Neurol., 1980, 50, 253;
(c) A. Tartara, A. Arrigo, C. Scamoni, and A. Presazzi,
Minerva Med., 1973, 64, 1943; (d) S. Banfi, W. Fonio,
E. Allievi, and S. Raimondo, Pharmacol. Res. Commun.,
1983, 15, 553.
3. (a) M. A. Enero, D. Solignac, and J. A. Apud, Clin. Exp.
Hypertens A, 1988, 10, Suppl 1, 331; (b) K. Kamei, Toho
Igakkai Zasshi, 1978, 25, 64; Chem. Abstr., 1978, 89, 140626.
4. (a) J. Nakao, T. Hasegawa, H. Hashimoto, T. Noto, and
T. Nakajima, Pharmacol. Biochem. Behav., 1991, 40, 359;
(b) J. Nakao, Kyotoꢀfuritsu Ika Daigaku Zasshi, 1990, 99, 57;
Chem. Abstr., 1990, 113, 71657; (c) K. Matsushita, L. R.
Gjessing, T. Shinka, and I. Matsumoto, Iyo Masu Kenkyukai
Koenshu, 1979, 4, 269; Chem. Abstr., 1980, 92, 142809;
(d) G. Nistico, Int. J. Clin. Pharmacol. Biopharm.,
1977, 15, 19.
3
–
1
C(3)), 20.7 (C(2)). IR (KBr), ν/cm : 2249 (CN).
ꢀAzidoꢀ3ꢀhydroxybutyronitrile (5). NaN3 (2.90 g,
4.6 mmol) and NH Cl (2.40 g, 44.8 mmol) were added to a
4
4
4
solution of 2ꢀoxiranylacetonitrile 4 (3.00 g, 36.1 mmol) in 80%
aqueous EtOH (50 mL). The resulting mixture was refluxed for
2
organic phase was extracted with Et O (2×50 mL), dried
(
trile 5 as a yellow oil (3.87 g, 85%). 4ꢀAzidoꢀ3ꢀhydroxybutyroꢀ
nitrile (5) had at least 95% purity ( H NMR) and was used
4 h. The reaction mixture was poured into water (100 mL). The
2
MgSO ), and evaporated to give 4ꢀazidoꢀ3ꢀhydroxybutyroniꢀ
4
1
8
1
1
without further purification in the next reaction. H NMR
(
CDCl ), δ: 4.19—4.03 (sextet, after exchange with D O quinꢀ
3
2
tet, 1 H, H(3), J = 5.5 Hz); 3.67 (d, 1 H, OH, J = 5.3 Hz); 3.41
d, 2 H, C(4)H , J = 5.1 Hz); 2.65 (d, 2 H, C(2)H , J = 5.9 Hz).
(
2
2
1
3
С NMR (CDCl ), δ: 116.9 (C(1)), 66.5 (C(3)), 55.1 (C(4)),
3
–
1
2
2
3.1 (C(2)). IR (KBr), ν/cm : 3438 (OH), 2289 (CN),
136 (N ).
3
4
ꢀAminoꢀ3ꢀhydroxybutyronitrile hydrochloride (6) was preꢀ
pared by hydrogenation of the respective azide by a modified
procedure.18 Into a 100ꢀmL flask were placed Pd/C (50 mg) and
4
ꢀazidoꢀ3ꢀhydroxybutyronitrile (5) (2.40 g, 19 mmol) in EtOH
5. E. Roberts, D. N. Krause, E. Wong, and A. Mori,
J. Neurosci., 1981, 1, 132.
(
50 mL) and CHCl (0.5 mL). A balloon filled with H gas (3 L)
3
2
was attached to the flask. The reaction mixture was hydrogeꢀ
nated for 24 h at 20 °C and under normal pressure. The catalyst
was removed by filtration. The filtrate was concentrated to give
6. F. M. Vaz and R. J. A. Wanders, Biochem. J., 2002, 361, 417.
7. (a) M. Tomita, Z. Physiol. Chem., 1923, 124, 253;
(b) M. Hayashi, M. Tomita, and K. Nagai, Jpn. Pat.
33000772, 1958; Chem. Abstr., 1959, 53, 1172cꢀe.
8. S. P. A. Italseber, Fr. Pat. 4329, 1966; Chem. Abstr., 1967,
67, 100415.
1
8
4
ꢀaminoꢀ3ꢀhydroxybutyronitrile hydrochloride (6) as a light
1
brown oil (2.50 g, 96%). H NMR (D O), δ: 4.24—4.15 (m, 1 H,
2
H(3)); 3.25—2.95 (m, 2 H, C(4)H ); 2.92—2.64 (m, 2 H,
2
13
C(2)H ). С NMR (D O), δ: 123.3 (C(1)), 68.3 (C(3)), 48.4
9. Y. Fujimoto and S. Koshimoto, Jpn. Pat. 46008682, 1971;
Chem. Abstr., 1971, 75, 36680.
2
2
–
1
(
C(4)), 28.4 (C(2)). IR (KBr), ν/cm : 3500—2900, 2261, 1612,